Gene transfer: anything goes in plant mitochondria

Parasitic plants and their hosts have proven remarkably adept at exchanging fragments of mitochondrial DNA. Two recent studies provide important mechanistic insights into the pattern, process and consequences of horizontal gene transfer, demonstrating that genes can be transferred in large chunks and that gene conversion between foreign and native genes leads to intragenic mosaicism. A model involving duplicative horizontal gene transfer and differential gene conversion is proposed as a hitherto unrecognized source of genetic diversity

The Breakdown of Alfven's Theorem in Ideal Plasma Flows

This paper presents both rigorous results and physical theory on the breakdown of magnetic flux conservation for ideal plasmas, by nonlinear effects. Our analysis is based upon an effective equation for magnetohydrodynamic (MHD) modes at length-scales $>\ell,$ with smaller scales eliminated, as in renormalization-group methodology. We prove that flux-conservation can be violated for an arbitrarily small length-scale $\ell,$ and in the absence of any non-ideality, but only if singular current sheets and vortex sheets both exist and intersect in sets of large enough dimension. This result gives analytical support to and rigorous constraints on theories of fast turbulent reconnection. Mathematically, our theorem is analogous to Onsager's result on energy dissipation anomaly in hydrodynamic turbulence. As a physical phenomenon, the breakdown of magnetic-flux conservation in ideal MHD is similar to the decay of magnetic flux through a narrow superconducting ring, by phase-slip of quantized flux lines. The effect should be observable both in numerical MHD simulations and in laboratory plasma experiments at moderately high magnetic Reynolds numbers.Comment: 38 pages, 1 figur

Ca. Nitrososphaera and Bradyrhizobium are inversely correlated and related to agricultural practices in long-term field experiments

Agricultural land management, such as fertilization, liming, and tillage affects soil properties, including pH, organic matter content, nitrification rates, and the microbial community. Three different study sites were used to identify microorganisms that correlate with agricultural land use and to determine which factors regulate the relative abundance of the microbial signatures of the agricultural land-use. The three sites included in this study are the Broadbalk Experiment at Rothamsted Research, UK, the Everglades Agricultural Area, Florida, USA, and the Kellogg Biological Station, Michigan, USA. The effects of agricultural management on the abundance and diversity of bacteria and archaea were determined using high throughput, barcoded 16S rRNA sequencing. In addition, the relative abundance of these organisms was correlated with soil features. Two groups of microorganisms involved in nitrogen cycle were highly correlated with land use at all three sites. The ammonia oxidizing-archaea, dominated by Ca. Nitrososphaera, were positively correlated with agriculture while a ubiquitous group of soil bacteria closely related to the diazotrophic symbiont, Bradyrhizobium, was negatively correlated with agricultural management. Analysis of successional plots showed that the abundance of ammonia oxidizing-archaea declined and the abundance of bradyrhizobia increased with time away from agriculture. This observation suggests that the effect of agriculture on the relative abundance of these genera is reversible. Soil pH and NH(3) concentrations were positively correlated with archaeal abundance but negatively correlated with the abundance of Bradyrhizobium. The high correlations of Ca. Nitrososphaera and Bradyrhizobium abundances with agricultural management at three long-term experiments with different edaphoclimatic conditions allowed us to suggest these two genera as signature microorganisms for agricultural land use

Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery

In this article we propose a systematic development method for rational drug design while reviewing paradigms in industry, emerging techniques and technologies in the field. Although the process of drug development today has been accelerated by emergence of computational methodologies, it is a herculean challenge requiring exorbitant resources; and often fails to yield clinically viable results. The current paradigm of target based drug design is often misguided and tends to yield compounds that have poor absorption, distribution, metabolism, and excretion, toxicology (ADMET) properties. Therefore, an in vivo organism based approach allowing for a multidisciplinary inquiry into potent and selective molecules is an excellent place to begin rational drug design. We will review how organisms like the zebrafish and Caenorhabditis elegans can not only be starting points, but can be used at various steps of the drug development process from target identification to pre-clinical trial models. This systems biology based approach paired with the power of computational biology; genetics and developmental biology provide a methodological framework to avoid the pitfalls of traditional target based drug design

A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with less than or equal to 30% blasts

Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts. The MTD was not reached; the RP2D was PAN 30 mg plus AZA 75 mg/m2. More patients receiving PAN+AZA achieved a composite complete response ([CR)+morphologic CR with incomplete blood count+bone marrow CR (27.5% (95% CI, 14.6–43.9%)) vs AZA (14.3% (5.4–28.5%)). However, no significant difference was observed in the 1-year OS rate (PAN+AZA, 60% (50–80%); AZA, 70% (50–80%)) or time to progression (PAN+AZA, 70% (40–90%); AZA, 70% (40–80%)). More grade 3/4 adverse events (97.4 vs 81.0%) and on-treatment deaths (13.2 vs 4.8%) occurred with PAN+AZA. Further dose or schedule optimization may improve the risk/benefit profile of this regimen

Temporal variations of vegetative features, sex ratios and reproductive phenology in a Dictyota dichotoma (Dictyotales, Phaeophyceae) population of Argentina

This paper addresses the phenology of a Dictyota dichotoma population from the North Patagonian coasts of Argentina. The morphology of the individuals was characterized, and analyses of the temporal variations of vegetative features, diploid and haploid life cycle generations and sex ratios are provided. Individuals, represented by growing sporophytes and gametophytes, occurred simultaneously throughout the year. Morphological variables showed temporal variation, except the width and height of medullary cells, which did not vary between seasons. All vegetative variables were significantly correlated with daylength. Besides, frond length, frond dry mass and apical and basal branching angles were significantly correlated with seawater temperatures. Vegetative thalli were less abundant than haploid and diploid thalli. Sporophytes were less abundant than male and female gametophytes. Male gametophytes dominated in May, August, October and January, and female gametophytes were more abundant in September, November, December, February and March. The formation of female gametangia showed a significant correlation with daylength, and the highest number of gametangia was registered in spring. In general, the male/female sex ratio varied between 1:2 and 1:1. Apical regions were more fertile than basal regions. Our data about frequency in the formation of reproductive structures and male/female ratios are the first recorded in the Dictyota genus and thus could not be compared with populations from other regions of the world. Significant morphological variation was observed in thalli of both life cycle generations, regarding length and dry mass, number of primary branches and branching basal angle. In general, all variables analyzed varied seasonally except cortical cell width.Fil: Gauna, Maria Cecilia. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Laboratorio de Ecología Acuática; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto Argentino de Oceanografía (i); ArgentinaFil: Caceres, Eduardo Jorge. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Laboratorio de Ficología y Micología; ArgentinaFil: Parodi, Elisa Rosalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto Argentino de Oceanografía (i); Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Laboratorio de Ecología Acuática; Argentin

Comparative Economic Evaluation of Haemophilus influenzae Type b Vaccination in Belarus and Uzbekistan

BACKGROUND: Hib vaccine has gradually been introduced into more and more countries during the past two decades, partly due to GAVI Alliance support to low-income countries. However, since Hib disease burden is difficult to establish in settings with limited diagnostic capacities and since the vaccine continues to be relatively expensive, some Governments remain doubtful about its value leading to concerns about financial sustainability. Similarly, several middle-income countries have not introduced the vaccine. The aim of this study is to estimate and compare the cost-effectiveness of Hib vaccination in a country relying on self-financing (Belarus) and a country eligible for GAVI Alliance support (Uzbekistan). METHODS AND FINDINGS: A decision analytic model was used to estimate morbidity and mortality from Hib meningitis, Hib pneumonia and other types of Hib disease with and without the vaccine. Treatment costs were attached to each disease event. Data on disease incidence, case fatality ratios and costs were primarily determined from national sources. For the Belarus 2009 birth cohort, Hib vaccine is estimated to prevent 467 invasive disease cases, 4 cases of meningitis sequelae, and 3 deaths, while in Uzbekistan 3,069 invasive cases, 34 sequelae cases and 341 deaths are prevented. Estimated costs per discounted DALY averted are US$9,323 in Belarus and US$ 267 in Uzbekistan. CONCLUSION: The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden. Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus. However, when seen in the context of the relative ability to pay for public health, the vaccine can be considered cost-effective in both countries